Stereochemistry of transition metal catalyzed asymmetric intramolecular allyl transfer in chiral α-sulfinyl allylic esters

Article abstract of DOI:10.1016/S0957-4166(01)00030-1

The stereochemistry of palladium or nickel catalyzed asymmetric intramolecular allyl transfer in chiral α-sulfinyl allylic esters was determined. The participation of the catalyst and the chiral sulfinyl functionality in these transformations, presumably by the coordination of the sulfinyl group to the catalyst, is discussed, and a novel mechanism is proposed for the rationalization of the results obtained.

Full text of DOI:10.1016/S0957-4166(01)00030-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 37–40
Stereochemistry of transition metal catalyzed asymmetric
intramolecular allyl transfer in chiral a-sulfinyl allylic esters
Kunio Hiroi,* Yoshio Suzuki, Fumiko Kato and Yoshiko Kyo
Department of Synthetic Organic Chemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai,
Miyagi 981-8558, Japan
Received 4 December 2000; accepted 11 January 2001
Abstract—The stereochemistry of palladium or nickel catalyzed asymmetric intramolecular allyl transfer in chiral a-sulfinyl allylic
esters was determined. The participation of the catalyst and the chiral sulfinyl functionality in these transformations, presumably
by the coordination of the sulfinyl group to the catalyst, is discussed, and a novel mechanism is proposed for the rationalization
of the results obtained. © 2001 Elsevier Science Ltd. All rights reserved.
Transition metal catalyzed reactions have received
much attention in recent years for achieving car-
bonꢀcarbon bond forming reactions with high stereo-
selectivity, owing to the availability of milder reaction
conditions with these catalysts.1 Currently, we are
developing a number of methods for asymmetric syn-
thesis with transition metal catalysts,2 especially those
using a chiral organosulfur functionality.3 Our recent
research has been focused on the incorporation of a
chiral sulfinyl moiety into transition metal catalysts. We
wish to communicate herein our recent work concern-
ing transition metal catalyzed intramolecular allyl
transfer in chiral a-sulfinyl allylic esters, we propose a
novel mechanism for allyl transfer in this system on the
basis of our observations on the stereochemistry of the
reactions.
rearrangements4 and the intramolecular nucleophilic
substitutions of p-allyl transition metal complexes.
Introduction of a chiral sulfinyl functionality into the
reaction substrates and stereochemical studies with
these substrates have enabled us to reveal the correct
reaction path and the mechanism of asymmetric induc-
tion, particularly with respect to participation of the
chiral sulfinyl groups in the transition metal catalysts.
Upon treatment with a palladium or nickel catalyst, the
chiral 2-(p-toluenesulfinyl)propionic allylic esters (Rs)-
1a and 1b, underwent asymmetric intramolecular allyl
transfer reactions to give a-allylic propionic esters with
high diastereoselectivity. After chiral a-sulfinyl propi-
onic allyl ester (Rs)-1a was treated with sec-butyl-
lithium or lithium diisopropylamide (LDA) (1.0 equiv.),
the reactions of the lithium enolate generated were
carried out in THF in the presence of Pd(PPh3)4 (0.1
equiv.) and PPh3 (0.2 equiv.), followed by treatment
Another interest focuses on two possible reaction paths
in the transition metal catalyzed reactions of allylic
esters, transition metal assisted [3,3]-sigmatropic
Scheme 1.
* Corresponding author. E-mail: khiroi@tohoku-pharm.ac.jp
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00030-1

38
K. Hiroi et al. / Tetrahedron: Asymmetry 12 (2001) 37–40
with (trimethylsilyl)diazomethane, to give (2S,Ss)-2a
(Scheme 1) with very high diastereoselectivity (85–94%),
as listed in Table 1.
lyl)diazomethane, to afford (2S,Ss)-2a in 18% yield
with high 87% diastereoselectivity.
The diastereomeric excess (d.e.) of the products was
calculated by HPLC analysis with ODS. The results
obtained are summarized in Table 1.
The palladium catalyzed reactions of the lithium eno-
late of the chiral a-sulfinyl propionic crotyl ester (Rs)-
1b (generated by treating with sec-butyllithium or
LDA) were carried out in THF at −20°C to furnish
exclusively (2S,Ss)-2b with good diastereoselectivity of
79%. On raising the reaction temperature to 0°C, an
excellent d.e. of 98–99% was observed. Both reactions
proceeded without formation of the [3,3]-sigmatropic
rearrangement product, methyl 2,3-dimethyl-2-(p-
toluenesulfinyl)-4-pentenoate.
For comparison, intermolecular asymmetric allylations
of methyl (Rs)-2-(p-toluenesulfinyl)propionate 3 with
or without a palladium catalyst were studied. The
lithium enolate of (Rs)-3 (generated by treating with
sec-butyllithium) was reacted with allyl acetate (2.0
equiv.) in THF at room temperature, 0 and −20°C in
the presence of Pd(PPh3)4 (0.2 equiv.) and PPh3 (0.4
equiv.) to afford (2S,Ss)-2a with 4% d.e. obtained at
room temperature. The d.e. increased to 37% in the 0°C
reaction, and unexpectedly (2R,Ss)-2a was formed at
−20°C with 15% d.e. The reaction at −78°C provided
no allylated product.
It should be noted, however, that the nickel catalyzed
reaction of the lithium enolate of (Rs)-1a gave an
allylated product with the same absolute configuration
to that obtained by a similar palladium catalyzed reac-
tion; the reaction of (Rs)-1a was carried out in THF at
room temperature in the presence of bis(cyclooctadi-
enyl)nickel [Ni(COD)2] (0.1 equiv.) and PPh3 (0.2
equiv.), followed by treatment with (trimethylsi-
The allylation reaction of (Rs)-3 with allyl bromide (1.5
equiv.) in THF at 0°C in the absence of a palladium
catalyst gave the unexpected (2R,Ss)-2a in 57% yield
Table 1. Transition metal catalyzed asymmetric intramolecular allyl transfer in chiral a-sulfinyl allylic esters (Rs)-1a,ba
Base
Reaction temp. (°C)
Yield (%) of (2S,Ss)-2a,b
D.e. (%) of (2S,Ss)-2a,bb
(Rs)-1a
(Rs)-1b
sec-BuLi
sec-BuLi
LDA
sec-BuLi
sec-BuLi
sec-BuLi
LDA
0
−20
0
Rt
−20
0
40
32
54
18c
31
73
32
85
94
94
87
79
98
99
0
a The reactions of (Rs)-1a,b were carried out in THF for 12 h in the presence of Pd(PPh3)4 (0.1 equiv.) and PPh3 (0.2 equiv.), followed by
treatment with (trimethylsilyl)diazomethane.
b The diastereomeric excess (d.e.) of (2S,Ss)-2a,b was calculated by HPLC analysis with ODS.
c
The reaction of (Rs)-1a was carried out in THF for 12 h in the presence of Ni(COD)2 (0.1 equiv.) and PPh3 (0.2 equiv.), followed by treatment
with (trimethylsilyl)diazomethane.
Scheme 2.
Table 2. Palladium catalyzed intermolecular asymmetric allylations of (Rs)-3a
Reaction temp. (°C)
Reaction time (h)
Yield (%) of (Ss)-2a
D.e. (%) of (Ss)-2a
Rt
6
7
17
12
17
38
49
28
–
4 (2S)
37 (2S)
15 (2R)
–
0
−20
−78
0
57b
39 (2R)
a The lithium enolate, generated from (Rs)-3 and sec-BuLi (1.2 equiv.), reacted with allyl acetate (2.0 equiv.) in THF in the presence of Pd(PPh3)4
(0.2 equiv.) and PPh3 (0.4 equiv.).
b The reaction of the lithium enolate of (Rs)-3 with allyl bromide (1.5 equiv.) was carried out in THF without the palladium catalyst.

K. Hiroi et al. / Tetrahedron: Asymmetry 12 (2001) 37–40
39
Scheme 3.
On the basis of the above-mentioned rationalization of
the intermolecular allylation, the intramolecular palla-
dium catalyzed reaction is elucidated as follows. There
are two possible reaction paths in palladium catalyzed
reactions of allylic ester enolates as mentioned before
(no thermal [3,3]-sigmatropic rearrangement occurred
under the mild reaction conditions employed in these
models). It should certainly be concluded that allylic
ester enolates undergo intramolecular allylation of ester
enolates via p-allyl-metal complexes, upon treatment
with a palladium or nickel catalyst, since the palladium
catalyzed reaction of the lithium enolate of (Ss)-1b
provided exclusively 2b without any formation of the
Claisen rearrangement product.
with 39% diastereoselectivity (Scheme 2). The results
obtained are summarized in Table 2.
The absolute configuration of the product, 2a, was
determined by chemical correlation to 3-methyl-3-
hexen-2-ol 8 of known absolute configuration5 as fol-
lows. The product (2S,Ss)-2a obtained by the
palladium catalyzed reaction of (Ss)-1a was reduced
with LiAlH4 to give alcohol (S)-(−)-4, oxidation with
CrO3–pyridine, followed by condensation of the alde-
hyde (S)-(−)-5 obtained with triphenylphosphine
methylide in a Wittig reaction gave (S)-(−)-6. Reduc-
tion of the olefin (S)-(−)-6 with diimide afforded sulfide
(R)-(−)-7, which was chemically correlated to (R)-(+)-8
of known absolute configuration5 by nucleophilic sub-
stitution of a mesylate of (R)-(+)-8 with sodium p-
toluenethiolate, which occurred with inversion of
configuration to yield (S)-(+)-7 (Scheme 3).
Further studies using a reaction substrate incorporating
deuterium atoms reveal that the most plausible reaction
path should be a course via p-allyl metal complexes,
not by [3,3]-sigmatropic rearrangements; the palladium
catalyzed reactions of 1,1-dideuterioallyl 2-p-toluene-
sulfonylpropionate 11 provided a 1:1 mixture of 3,3- or
5,5-dideuterio-2-methyl-2-(p-toluenesulfonyl)-4-pen-
tenoic acids 12a and 12b (Scheme 5).
The results obtained can be rationalized by the follow-
ing mechanism: the intermolecular allylation of (Rs)-3
with allyl bromide at 0°C in THF using LDA as a base
would proceed via a lithium chelate of the enolate
(Ss)-9 coordinated by the sulfinyl oxygen atoms, the
formation of chelates of lithium or magnesium enolates
with sulfinyl oxygen atoms has precedence from many
investigators.6 Allyl bromide attacks from the less
crowded lone pair side of the sulfinyl group to give
(2R,Ss)-2a in 57% yield with 39% d.e. The palladium
catalyzed allylation of the enolate of (Rs)-3 with allyl
acetate would proceed via a different reaction path; at
−20°C, the reaction would occur via (Ss)-9 in a similar
way to the reaction with allyl bromide, giving (2R,Ss)-
2a with low d.e. of 15%, whereas the allylation reaction
at higher temperatures (0°C or room temperature)
would proceed via the palladium chelate 10 (Scheme 4)
obtained by transmetallation of the lithium enolate
with a palladium catalyst and coordination of a chiral
sulfinyl sulfur atom,3e presumably by intramolecular or
intermolecular allylation with a p-allyl-palladium com-
plex as an allylating reagent from the sterically less
crowded (sulfinyl oxygen downward) side, giving
(2S,Ss)-2a in 38 or 49% yield with 4 or 37% d.e.,
Thus, as designated in Scheme 6, the intramolecular
allylation via (Ss)-13a from the sterically less crowded
sulfinyl sulfur lone pair side provides (2R,Ss)-2a. How-
ever, the explanation via a path involving (Ss)-13a is in
conflict with the experimental result. Therefore, it
should be certainly assumed that the reaction proceeds
via a palladium chelate (Ss)-13c, obtained through
equilibrium via an enolate (Ss)-13b, coordinated by a
chiral sulfinyl sulfur atom.3e Here, the allylation would
occur from the less sterically crowded (sulfinyl oxygen
respectively.
.
Scheme 4.

40
K. Hiroi et al. / Tetrahedron: Asymmetry 12 (2001) 37–40
Scheme 5.
Scheme 6.
upward) side of the preferred conformer (Ss)-13c1 in
the conformational equilibrium of the five-membered
palladium complex, providing (2S,Ss)-2a.
153–156; (b) Hiroi, K.; Kato, F.; Nakasato, H. Chem.
Lett. 1998, 553–554; (c) Hiroi, K.; Suzuki, Y. Tetrahedron
Lett. 1998, 39, 6499–6502; (d) Hiroi, K.; Suzuki, Y.; Abe,
I.; Hasegawa, Y.; Suzuki, K. Tetrahedron: Asymmetry
1998, 9, 3797–3817; (e) Hiroi, K.; Suzuki, Y.; Kawagishi,
R. Tetrahedron Lett. 1999, 40, 715–718; (f) Hiroi, K.;
Yoshida, Y.; Kaneko, Y. Tetrahedron Lett. 1999, 40, 3431–
3434; (g) Hiroi, K.; Suzuki, Y.; Abe, I.; Kawagishi, R.
Tetrahedron 2000, 56, 4701–4710.
Extremely high enantioselectivity was observed in tran-
sition metal catalyzed asymmetric intramolecular allyl
transfer of chiral a-sulfinyl allylic esters. A novel mech-
anism is assumed for rationalization of the stereochem-
ical outcome obtained.
4. Tsuji, J. Palladium Reagents and Catalysts; John Wiley &
Sons: Chichester, 1995; pp. 400–404 and references cited
therein.
References
5. Kirmse, W.; Knist, J.; Ratajczak, H.-J. Chem. Ber. 1976,
109, 2296–2314.
1. (a) Brunner, H. Synthesis 1988, 645–654; (b) Blystone, S.
L. Chem. Rev. 1989, 1663–1679; (c) Ojima, I.; Clos, N.;
Bastos, C. Tetrahedron 1989, 45, 6901–6939; (d) Sawa-
mura, M.; Ito, Y. Chem. Rev. 1992, 92, 857–871.
2. (a) Hiroi, K.; Abe, J.; Suya, K.; Sato, S.; Koyama, T. J.
Org. Chem. 1994, 59, 203–213 and references cited therein;
(b) Hiroi, K.; Kato, F.; Yamagata, A. Chem. Lett. 1998,
397–398.
6. (a) Kunieda, N.; Nokami, J.; Kinoshita, M. Chem. Lett.
1974, 369–372; (b) Mioskowski, C.; Solladie, G. J. Chem.
Soc., Chem. Commun. 1977, 162–163; (c) Mioskowski, C.;
Solladie, G. Tetrahedron 1980, 36, 227–236; (d) Posner, G.
H.; Mallamo, J. P.; Miura, K. J. Am. Chem. Soc. 1981,
103, 2886–2887; (e) Solladie, G.; Matloubi-Mogadham, F.
J. Org. Chem. 1982, 47, 91–94.
3. (a) Hiroi, K.; Arinaga, Y. Tetrahedron Lett. 1994, 35,
.
.